The 400 MHz NMR spectrometer requested in this grant proposal is needed by the Chemistry Department at Rensselaer Polytechnic Institute to support several NIH-funded research programs. The core user group requires a high-field NMR instrument with sophisticated software to study large biochemicals such as proteins, polypeptides and related species as well as structurally complex "small" organic molecules. Specific applications include the study of 1) proteins (endothelin, alamethicin, gramicidin and ion-binding sites of lysozyme), 2) drug interactions with model oligonucleotides, 3) self-assembled inorganic double helicates that perform charge transfer functions somewhat analogous to photosynthetic systems, and 4) ion channels. Other biologically relevant projects under investigation include the study of polyether antibiotics, inhibitors of cholesterol biosynthesis, opiates, C-nucleosides that exhibit anti-AIDS activity, and glycoside antibiotics. Enantioselective methods for synthesis of organic molecules with biological and/or medicinal activity are being developed. High field NMR spectroscopy will play a crucial role in the understanding of stereocontrol mechanisms. New synthetic methods for the construction of complex macrocyclic systems are under development; these macrocycles will bind metal ions and small organic molecules and will enable stereoselective reactions to be carried out A high field NMR also will be invaluable for the development of new photoaffinity labels for the opiate receptors.